Neuromuscular structure of the tibialis anterior muscle for functional electrical stimulation.

Neuromuscular structure of the tibialis anterior muscle for functional electrical stimulation.

Surg Radiol Anat. 2016 May 20;

Authors: Yi KH, Cong L, Bae JH, Park ES, Rha DW, Kim HJ

Abstract
PURPOSE: This study describes the nerve entry points and intramuscular nerve branching of the tibialis anterior, providing essential information for therapeutic functional electrical stimulation and botulinum toxin injection.
METHODS: One hundred and ten legs from Korean and Thai cadavers were dissected. Ten specimens were harvested and subjected to modified Sihler's staining.
RESULTS: The average total length from the lateral malleolus to the fibular head was 32.0 cm (SD 1.9). The nerve entry points were densely distributed between 86.5 and 90.6 % of the reference length, where the first and second nerve entry points were observable. A densely arborizing area of the intramuscular nerve branches was observed at 70-80 % of the reference length.
CONCLUSIONS: Based on the results of this study, clinicians can increase the effectiveness of therapeutic functional electrical stimulation and identify the ideal sites for botulinum toxin injection to the tibialis anterior muscle.

PMID: 27206542 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/20m63Mw
via IFTTT

Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11.

Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11.

Oral Oncol. 2016 Jun;57:21-26

Authors: Ward MC, Adelstein DJ, Bhateja P, Nwizu TI, Scharpf J, Houston N, Lamarre ED, Lorenz R, Burkey BB, Greskovich JF, Koyfman SA

Abstract
PURPOSE: The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the timing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) develops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of SLD after CRT.
METHODS: Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT between 1993 and 2013 were identified. Events occurring beyond 3months after treatment and suggestive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered SLD. The cumulative incidence of SLD and its components was quantified using Gray's competing risk analysis with recurrence or death considered competing risks.
RESULTS: Eighty-four patients were included with a median follow-up of 43months. The 5-year overall survival was 70% (95% CI 58-80%). No death was directly a result of treatment-induced late dysphagia. The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within 5years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred beyond five years from CRT.
CONCLUSIONS: SLD is common after CRT for larynx cancer and can occur beyond 5years from the end of treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death related to dysphagia is uncommon.

PMID: 27208840 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YNVGAF
via IFTTT

Prevalence of oral health-related conditions that could trigger accidents for patients with moderate-to-severe dementia.

Prevalence of oral health-related conditions that could trigger accidents for patients with moderate-to-severe dementia.

Gerodontology. 2016 May 21;

Authors: Kobayashi N, Soga Y, Maekawa K, Kanda Y, Kobayashi E, Inoue H, Kanao A, Himuro Y, Fujiwara Y

Abstract
OBJECTIVE: This study was performed to determine the prevalence of oral health conditions unnoticed by doctors and ward staff that may increase risk of incidents and/or accidents in hospitalised patients with moderate-severe dementia.
BACKGROUND DATA DISCUSSING THE PRESENT STATUS OF THE FIELD: Dementia patients may not recognise risks in the mouth, such as tooth mobility or ill-fitting dental prostheses and/or dentures. In addition to the risk of choking, injury by sharp edges of collapsed teeth or prosthodontics could pose risks. However, many previous publications were limited to case reports or series.
MATERIALS AND METHODS: Ninety-two consecutive hospitalised dementia patients (M: 52, F: 40, median age: 82.5 years, range: 62-99 years, from 2011 to 2014), referred for dentistry for dysphagia rehabilitation, were enrolled in this study. Participants referred for dental treatment with dental problems detected by ward staff were excluded. All participants had a Global Clinical Dementia Rating Score >2. Their dental records were evaluated retrospectively for issues that may cause incidents and/or accidents.
RESULTS: Problems in the mouth, for example tooth stumps, dental caries, and ill-fitting dentures, were detected in 51.1% of participants (47/92). Furthermore, 23.9% (22/92) showed risk factors that could lead to incidents and/or accidents, for example falling out of teeth and/or prosthodontics or injury by sharp edges of teeth and/or prosthodontics.
CONCLUSIONS: Hospitalised moderate-severe dementia patients had a high prevalence of oral health conditions unnoticed by doctors and ward staff that may increase risk of incidents and/or accidents.

PMID: 27207609 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TP33DR
via IFTTT

[A Case of Giant Fibrovascular Polyp of the Esophagus, Treated Successfully by Endoscopic Resection].

[A Case of Giant Fibrovascular Polyp of the Esophagus, Treated Successfully by Endoscopic Resection].

Korean J Gastroenterol. 2016 May 25;67(5):253-256

Authors: Lee JW, Kim GH, Kim JK, Park CH, Song BG, Shin DH, Ha DW, Am Song G

Abstract
Fibrovascular polyps are rare benign intraluminal tumors that usually arise from the cervical esophagus. These often present as very large sized pedunculated polyps and cause symptoms including dysphagia and respiratory distress. Generally, large polyps are surgically excised, while endoscopic resection is limited to smaller polyps. Herein, we present a giant fibrovascular polyp of the esophagus treated successfully by endoscopic resection.

PMID: 27206436 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YNYwpp
via IFTTT

3D cerebral MR image segmentation using multiple-classifier system.

3D cerebral MR image segmentation using multiple-classifier system.

Med Biol Eng Comput. 2016 May 20;

Authors: Amiri S, Movahedi MM, Kazemi K, Parsaei H

Abstract
The three soft brain tissues white matter (WM), gray matter (GM), and cerebral spinal fluid (CSF) identified in a magnetic resonance (MR) image via image segmentation techniques can aid in structural and functional brain analysis, brain's anatomical structures measurement and visualization, neurodegenerative disorders diagnosis, and surgical planning and image-guided interventions, but only if obtained segmentation results are correct. This paper presents a multiple-classifier-based system for automatic brain tissue segmentation from cerebral MR images. The developed system categorizes each voxel of a given MR image as GM, WM, and CSF. The algorithm consists of preprocessing, feature extraction, and supervised classification steps. In the first step, intensity non-uniformity in a given MR image is corrected and then non-brain tissues such as skull, eyeballs, and skin are removed from the image. For each voxel, statistical features and non-statistical features were computed and used a feature vector representing the voxel. Three multilayer perceptron (MLP) neural networks trained using three different datasets were used as the base classifiers of the multiple-classifier system. The output of the base classifiers was fused using majority voting scheme. Evaluation of the proposed system was performed using Brainweb simulated MR images with different noise and intensity non-uniformity and internet brain segmentation repository (IBSR) real MR images. The quantitative assessment of the proposed method using Dice, Jaccard, and conformity coefficient metrics demonstrates improvement (around 5 % for CSF) in terms of accuracy as compared to single MLP classifier and the existing methods and tools such FSL-FAST and SPM. As accurately segmenting a MR image is of paramount importance for successfully promoting the clinical application of MR image segmentation techniques, the improvement obtained by using multiple-classifier-based system is encouraging.

PMID: 27207464 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1s2pHSS
via IFTTT

Clinical validation of automated audiometry with continuous noise-monitoring in a clinically heterogeneous population outside a sound-treated environment.

Clinical validation of automated audiometry with continuous noise-monitoring in a clinically heterogeneous population outside a sound-treated environment.

Int J Audiol. 2016 May 20;:1-7

Authors: Brennan-Jones CG, Eikelboom RH, Swanepoel W, Friedland PL, Atlas MD

Abstract
OBJECTIVE: Examine the accuracy of automated audiometry in a clinically heterogeneous population of adults using the KUDUwave automated audiometer.
DESIGN: Prospective accuracy study. Manual audiometry was performed in a sound-treated room and automated audiometry was not conducted in a sound-treated environment.
STUDY SAMPLE: 42 consecutively recruited participants from a tertiary otolaryngology department in Western Australia.
RESULTS: Absolute mean differences ranged between 5.12-9.68 dB (air-conduction) and 8.26-15 dB (bone-conduction). A total of 86.5% of manual and automated 4FAs were within 10 dB (i.e. ±5 dB); 94.8% were within 15 dB. However, there were significant (p < 0.05) differences between automated and manual audiometry at 250, 500, 1000, and 2000 Hz (air-conduction) and 500 and 1000 Hz (bone-conduction). The effect of age (≥55 years) on accuracy (p = 0.014) was not significant on linear regression (p > 0.05; R(2) =( ) 0.11). The presence of a hearing loss (better ear ≥26 dB) did not significantly affect accuracy (p = 0.604; air-conduction), (p = 0.218; bone-conduction).
CONCLUSIONS: This study provides clinical validation of automated audiometry using the KUDUwave in a clinically heterogeneous population, without the use of a sound-treated environment. Whilst threshold variations were statistically significant, future research is needed to ascertain the clinical significance of such variation.

PMID: 27206551 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1s2nl6B
via IFTTT

Signaling regulation and role of filamin A cleavage in Ca2+-stimulated migration of androgen receptor-deficient prostate cancer cells.

Signaling regulation and role of filamin A cleavage in Ca2+-stimulated migration of androgen receptor-deficient prostate cancer cells.

Oncotarget. 2016 May 19;

Authors: Huang C, Miller RT, Freter CE

Abstract
Ca2+, a ubiquitous cellular signal, and filamin A, an actin-binding protein, play an important role in the regulation of cell adhesion, shape and motility. Using transwell filters to analyze cell migration, we found that extracellular Ca2+ (Cao2+) promotes the migration of androgen receptor (AR)-deficient and highly metastatic prostate cancer cell lines (DU145 and PC-3) compared to AR-positive and relatively less metastatic prostate cancer cells (LNCaP). Furthermore, we found that expression of filamin A is up-regulated in DU145 and PC-3 cells, and that Cao2+ significantly induces the cleavage of filamin A. Silencing expression of Ca2+-sensing receptor (CaR) and p115RhoGEF, and treating with leupeptin, a protease inhibitor, and ALLM, a calpain specific inhibitor, we further demonstrate that Cao2+-induced filamin A cleavage occurs via a CaR- p115RhoGEF-calpain dependent pathway. Our data show that Cao2+ via CaR- mediated signaling induces filamin A cleavage and promotes the migration in AR-deficient and highly metastatic prostate cancer cells.

PMID: 27206800 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TvIdfC
via IFTTT

Sensitive and affordable diagnostic assay for the quantitative detection of anaplastic lymphoma kinase (ALK) alterations in patients with non-small cell lung cancer.

Sensitive and affordable diagnostic assay for the quantitative detection of anaplastic lymphoma kinase (ALK) alterations in patients with non-small cell lung cancer.

Oncotarget. 2016 May 19;

Authors: Dama E, Tillhon M, Bertalot G, de Santis F, Troglio F, Pessina S, Passaro A, Pece S, de Marinis F, Dell'Orto P, Viale G, Spaggiari L, Di Fiore PP, Bianchi F, Barberis M, Vecchi M

Abstract
Accurate detection of altered anaplastic lymphoma kinase (ALK) expression is critical for the selection of lung cancer patients eligible for ALK-targeted therapies. To overcome intrinsic limitations and discrepancies of currently available companion diagnostics for ALK, we developed a simple, affordable and objective PCR-based predictive model for the quantitative measurement of any ALK fusion as well as wild-type ALK upregulation. This method, optimized for low-quantity/-quality RNA from FFPE samples, combines cDNA pre-amplification with ad hoc generated calibration curves. All the models we derived yielded concordant predictions when applied to a cohort of 51 lung tumors, and correctly identified all 17 ALK FISH-positive and 33 of the 34 ALK FISH-negative samples. The one discrepant case was confirmed as positive by IHC, thus raising the accuracy of our test to 100%. Importantly, our method was accurate when using low amounts of input RNA (10 ng), also in FFPE samples with limited tumor cellularity (5-10%) and in FFPE cytology specimens. Thus, our test is an easily implementable diagnostic tool for the rapid, efficacious and cost-effective screening of ALK status in patients with lung cancer.

PMID: 27206799 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NENguZ
via IFTTT

Genome-wide DNA methylation profiles altered by Helicobacter pylori in gastric mucosa and blood leukocyte DNA.

Genome-wide DNA methylation profiles altered by Helicobacter pylori in gastric mucosa and blood leukocyte DNA.

Oncotarget. 2016 May 19;

Authors: Zhang Y, Zhang XR, Park JL, Kim JH, Zhang L, Ma JL, Liu WD, Deng DJ, You WC, Kim YS, Pan KF

Abstract
PURPOSE: To investigate Helicobacter pylori (H.pylori) associated genome-wide aberrant methylation patterns in gastric mucosa and blood leukocyte DNA, a population-based study was conducted in Linqu County.
RESULTS: A total of 3000 and 386 CpGs were differentially methylated after successful H.pylori eradication in gastric mucosa and blood leukocyte DNA respectively, and 17 were the same alteration trend in the both tissues. The differentially methylated CpGs were located more frequently in promoters or CpG islands for gastric mucosa and gene body or open sea for blood leukocyte DNA. In eradicated gastric mucosa, the hypermethylated CpGs were enriched across inflammatory pathways, while the hypomethylated CpGs in tube morphogenesis, development and so on. The final validation found lower SPI1, PRIC285 and S1PR4 methylation levels in H.pylori positive subjects by case-control comparison, and increased methylation levels in H.pylori eradicated gastric mucosa by self-comparison. The Cancer Genome Atlas (TCGA) database analysis suggested that the up-regulation of the three genes by hypomethylation might be associated with gastric carcinogenesis.
EXPERIMENTAL DESIGN: Infinium HumanMethylation 450K BeadChip was used to compare methylation profiles prior to and after eradication treatment. The methylation levels of identified candidate differentially methylated genes before and after H.pylori eradication were further validated by two stages (Stage I: self-comparison of 16 subjects before and after anti-H.pylori treatment; Stage II: case-control comparison of 25 H.pylori positive and 25 negative subjects and self-comparison of 50 anti-H.pylori treated subjects).
CONCLUSIONS: Novel H.pylori associated aberrant methylated genes were identified across the whole genome both in gastric mucosa and blood leukocyte DNA.

PMID: 27206798 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1s2poHH
via IFTTT

Pseudomonas aeruginosa mannose-sensitive hemagglutinin inhibits proliferation and invasion via the PTEN/AKT pathway in HeLa cells.

Pseudomonas aeruginosa mannose-sensitive hemagglutinin inhibits proliferation and invasion via the PTEN/AKT pathway in HeLa cells.

Oncotarget. 2016 May 19;

Authors: Yin TQ, Ou-Yang X, Jiao FY, Huang LP, Tang XD, Ren BQ

Abstract
We investigated the effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the proliferation and invasion of human cervical cancer cell lines, as well as the molecular pathways underlying these effects. MTT cell proliferation assays revealed a time- and concentration-dependent cytotoxic effect of PA-MSHA on HeLa cells but not H8 cells. Flow cytometry with propidium iodide and annexin-V-fluorescein isothiocyanate labeling (FITC) indicated that various concentrations of PA-MSHA could induce apoptosis and G2-M cell cycle arrest in HeLa cells. PA-MSHA also impaired the migration and invasion abilities of HeLa cells in Wound healing and Transwell invasion assays. Western blot results demonstrated that PA-MSHA reduced the expression of p-AKT, p-GSK3β, BCL-2, Vimentin and β-catenin, but increased the levels of PTEN, BAD, BAX and E-cadherin in HeLa cells. Importantly, PTEN siRNA induced the activity of p-AKT, while PA-MSHA partly inhibited this induction, indicating that PA-MSHA may reduce the cell proliferation and invasion potential by activating PTEN and thus inhibiting the AKT pathway in vitro. These data suggest the potential application of PA-MSHA to the treatment of human cervical cancer.

PMID: 27206797 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TvIsXV
via IFTTT

The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth.

The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth.

Oncotarget. 2016 May 19;

Authors: Trousil S, Kaliszczak M, Schug Z, Nguyen Q, Tomasi G, Favicchio R, Brickute D, Fortt R, Twyman FJ, Carroll L, Kalusa A, Navaratnam N, Adejumo T, Carling D, Gottlieb E, Aboagye EO

Abstract
The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2-2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids.

PMID: 27206796 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1s2plM5
via IFTTT

Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells.

Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells.

Oncotarget. 2016 May 18;

Authors: Zhang W, Bao L, Yang S, Qian Z, Dong M, Yin L, Zhao Q, Ge K, Deng Z, Zhang J, Qi F, An Z, Yu Y, Wang Q, Wu R, Fan F, Zhang L, Chen X, Na Y, Feng L, Liu L, Zhu Y, Qin T, Zhang S, Zhang Y, Zhang X, Wang J, Yi X, Zou L, Xin HW, Ditzel HJ, Gao H, Zhang K, Liu B, Cheng S

Abstract
Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326 blood samples from patients with 6 different solid organ carcinomas and lymphomas. Significantly, CTC-positive rates increased remarkably with tumor progression from N0M0, N+M0 to M1 in each of 5 tested cancers (lung, colon, liver, gastric and pancreatic cancer, and glioma). Among 21 non-small cell lung cancer cases in which CTC values were consecutively monitored, 81% showed treatment-related decreases, which was also found after treatments in the other solid tumors. Moreover, monitoring CTC values provided an efficient treatment response indicator in hematological malignancies. Compared to CellSearch, our method detected significantly higher positive rates in 40 NSCLC in all stages, including N0M0, N+M0 and M1, and was less affected by chemotherapy. This simple, robust and clinically-applicable technology detects viable CTCs from solid and hematopoietic malignancies in early to late stages, and significantly improves clinical detection and treatment prognostication.

PMID: 27206795 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TnuLxs
via IFTTT

TSH inhibits SERCA2a and the PKA/PLN pathway in rat cardiomyocytes.

TSH inhibits SERCA2a and the PKA/PLN pathway in rat cardiomyocytes.

Oncotarget. 2016 May 16;

Authors: Dong J, Gao C, Liu J, Cao Y, Tian L

Abstract
Elevated thyroid-stimulating hormone (TSH) levels often accompany impaired LV diastolic function and subtle systolic dysfunction in subclinical hypothyroidism (sHT). These cardiac dysfunctions are characterized by increases in mean aortic acceleration and pre-ejection/ejection time ratios. To explore the mechanism underlying these pathologies, we investigated the effects of TSH on sarcoplasmic reticulum calcium ATPase (SERCA2a) activity and expression in neonatal rat cardiomyocytes. TSH inhibited SERCA2a activity and expression by binding to TSH receptors in cardiomyocyte membranes and inhibiting the protein kinase A/phoshpolamban (PKA/PLN) signaling pathway. These results suggest that increases in serum TSH levels contribute to the development of cardiac diastolic and systolic dysfunction.

PMID: 27206677 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1OGPUuZ
via IFTTT

The inflammasome: an emerging therapeutic oncotarget for cancer prevention.

The inflammasome: an emerging therapeutic oncotarget for cancer prevention.

Oncotarget. 2016 May 17;

Authors: Zhiyu W, Wang N, Wang Q, Peng C, Zhang J, Liu P, Ou A, Zhong S, Cordero MD, Lin Y

Abstract
Deregulated inflammation is considered to be one of the hallmarks of cancer initiation and development regulation. Emerging evidence indicates that the inflammasome plays a central role in regulating immune cells and cytokines related to cancer. The inflammasome is a multimeric complex consisting of Nod-like receptors (NLRs) and responds to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli. Several lines of evidence suggests that in cancer the inflammasome is positively associated with characteristics such as elevated levels of IL-1β and IL-18, activation of NF-κB signaling, enhanced mitochondrial oxidative stress, and activation of autophagic process. A number of NLRs, such as NLRP3 and NLRC4 are also highlighted in carcinogenesis and closely correlate to chemoresponse and prognosis. Although conflicting evidence suggested the duplex role of inflammasome in cancer development, the phenomenon might be attributed to NLRs difference, cell and tissue type, cancer stage, and specific experimental conditions. Given the promising role of inflammasome in mediating cancer development, precise elucidation of its signaling network and pathological significance may lead to novel therapeutic options for malignancy therapy and prevention.

PMID: 27206676 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1WK9X4g
via IFTTT

Loss of T-cell quiescence by targeting Slfn2 prevents the development and progression of T-ALL.

Loss of T-cell quiescence by targeting Slfn2 prevents the development and progression of T-ALL.

Oncotarget. 2016 May 17;

Authors: Goldshtein A, Zerbib SM, Omar I, Cohen-Daniel L, Popkin D, Berger M

Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Despite significant improvement in the treatment of T-ALL, approximately 20% of children and most adults undergo relapse. Previous findings demonstrated that loss of T-cell quiescence due to a mutation in the Slfn2 gene (elektra) leads to acquisition of an aberrant developmental program by which T-cells lose their renewal capabilities and undergo apoptosis. Here we show that the elektra mutation in Slfn2 completely prevents a severe lymphoproliferative disease caused by overexpression of BCL2 in combination with Fas deficiency in mice. Moreover, Slfn2 impaired-function protects mice from experimental disease similar to human T-ALL by severely impairing the proliferation potential and survival of leukemic T-cells, partially by activation of the p53 tumor suppressor protein. Our study suggest that in certain malignancies, such as T-ALL, a novel therapeutic strategy may be applied by imposing aberrant development of leukemic cells. Furthermore, as the elektra mutation in Slfn2 seems to impair only T-cells and monocytes, targeting Slfn2 is expected to be harmless to other cell types, and thereby could be a promising target for treating malignancies. Together our results demonstrate the potential of targeting Slfn2 and its human paralog for T-ALL treatment.

PMID: 27206675 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TvIPSc
via IFTTT

Are TKIs favourable for the elderly with non-small-cell lung cancer?

Are TKIs favourable for the elderly with non-small-cell lung cancer?

Oncotarget. 2016 May 17;

Authors: Rossi S, D'Argento E, Schinzari G, Dadduzio V, Di Noia V, Cassano A, Barone C

Abstract
Background - Epidermal Growth Factor Receptor (EGFR) tyrosine-kinase inhibitors (TKIs) have changed treatment strategies for patients with advanced non-small-cell lung cancer (NSCLC) harbouring mutations in EGFR gene. This retrospective analysis assessed efficacy and safety of TKIs in elderly compared to younger patients.Patients and methods - 49 patients with advanced NSCLC and mutations in exon 19 or 21 receiving a first-line therapy with TKIs were included and divided into patients aged <70 years and patients aged ≥ 70 years. Primary endpoints were progression free survival (PFS), response rate (RR) and clinical benefit in terms of quality of life; secondary endpoint was overall survival (OS).Results - Median PFS was significantly longer in elderly in comparison to younger patients (12.6 and 5.6 months, respectively; p= .008). RR was 64% in younger patients and 75% in elderly population. Eighteen out of 20(90%) elderly patients treated with gefitinib experienced symptoms relief and upgrading of performance status. No difference in terms of OS was found (p= .34).Conclusion - TKIs seem more effective in elderly than in younger patients affected by NSCLC with an EGFR gene mutation. We hypothesize that the main difference between the two populations is the number of medications related to concomitant comorbidities that cause an increased plasma level of TKIs.

PMID: 27206674 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1s2pDCM
via IFTTT

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Upregulation of antioxidant genes correlates with regression of melanoma malignancy and with malignant progression when downregulated.

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Upregulation of antioxidant genes correlates with regression of melanoma malignancy and with malignant progression when downregulated.

Oncotarget. 2016 May 10;

Authors: Bracalente C, Ibañez IL, Berenstein A, Notcovich C, Cerda MB, Klamt F, Chernomoretz A, Durán H

Abstract
Reactive oxygen species (ROS) are implicated in tumor transformation. The antioxidant system (AOS) protects cells from ROS damage. However, it is also hijacked by cancers cells to proliferate within the tumor. Thus, identifying proteins altered by redox imbalance in cancer cells is an attractive prognostic and therapeutic tool. Gene expression microarrays in A375 melanoma cells with different ROS levels after overexpressing catalase were performed. Dissimilar phenotypes by differential compensation to hydrogen peroxide scavenging were generated. The melanotic A375-A7 (A7) upregulated TYRP1, CNTN1 and UCHL1 promoting melanogenesis. The metastatic A375-G10 (G10) downregulated MTSS1 and TIAM1, proteins absent in metastasis. Moreover, differential coexpression of AOS genes (EPHX2, GSTM3, MGST1, MSRA, TXNRD3, MGST3 and GSR) was found in A7 and G10. Their increase in A7 improved its AOS ability and therefore, oxidative stress response, resembling less aggressive tumor cells. Meanwhile, their decrease in G10 revealed a disruption in the AOS and therefore, enhanced its metastatic capacity.These gene signatures, not only bring new insights into the physiopathology of melanoma, but also could be relevant in clinical prognostic to classify between non aggressive and metastatic melanomas.

PMID: 27206673 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TvIyyG
via IFTTT

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis.

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis.

Oncotarget. 2016 May 7;

Authors: Bracalente C, Salguero N, Notcovich C, Müller CB, da Motta LL, Klamt F, Ibañez IL, Durán H

Abstract
Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy.

PMID: 27206672 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1s2pNK9
via IFTTT

Enhancement of aging rat laryngeal muscles with endogenous growth factor treatment.

Enhancement of aging rat laryngeal muscles with endogenous growth factor treatment.

Physiol Rep. 2016 May;4(10)

Authors: Stemple JC, Andreatta RD, Seward TS, Angadi V, Dietrich M, McMullen CA

Abstract
Clinical evidence suggests that laryngeal muscle dysfunction is associated with human aging. Studies in animal models have reported morphological changes consistent with denervation in laryngeal muscles with age. Life-long laryngeal muscle activity relies on cytoskeletal integrity and nerve-muscle communication at the neuromuscular junction (NMJ). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. We hypothesized that treatment with neurotrophin 4 (NTF4) would modify the morphology and functional innervation of aging rat laryngeal muscles. Fifty-six Fischer 344xBrown Norway rats (6- and 30-mo age groups) were used to evaluate to determine if NTF4, given systemically (n = 32) or directly (n = 24), would improve the morphology and functional innervation of aging rat thyroarytenoid muscles. Results demonstrate the ability of rat laryngeal muscles to remodel in response to neurotrophin application. Changes were demonstrated in fiber size, glycolytic capacity, mitochondrial, tyrosine kinase receptors (Trk), NMJ content, and denervation in aging rat thyroarytenoid muscles. This study suggests that growth factors may have therapeutic potential to ameliorate aging-related laryngeal muscle dysfunction.

PMID: 27207784 [PubMed]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/27N6Yvg
via IFTTT

Treatment of advanced thyroid cancer with targeted therapies: ten years of experience.

Treatment of advanced thyroid cancer with targeted therapies: ten years of experience.

Endocr Relat Cancer. 2016 Apr;23(4):R185-R205

Authors: Viola D, Valerio L, Molinaro E, Agate L, Bottici V, Biagini A, Lorusso L, Cappagli V, Pieruzzi L, Giani C, Sabini E, Passannati P, Puleo L, Matrone A, Pontillo-Contillo B, Battaglia V, Mazzeo S, Vitti P, Elisei R

Abstract
Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.

PMID: 27207700 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U6XHXk
via IFTTT

Completion lobectomy after radical segmentectomy for pulmonary malignancies.

Completion lobectomy after radical segmentectomy for pulmonary malignancies.

Asian Cardiovasc Thorac Ann. 2016 Jun;24(5):450-4

Authors: Omasa M, Date H, Takamochi K, Suzuki K, Miyata Y, Okada M

Abstract
OBJECTIVE: Completion lobectomy after radical segmentectomy is relatively rare, with no systematic evaluation of this challenging procedure. We aimed to clarify the details of this operation performed in 3 Japanese institutions.
METHODS: Completion lobectomy after segmentectomy in the same lobe was performed in 11 patients (9 lung cancers and 2 metastatic lung tumors) between 2007 and 2013. Surgical outcomes were analyzed retrospectively.
RESULTS: The 11 patients accounted for 1.37% of the 805 segmentectomies performed in the 3 institutions. The reasons for completion lobectomy were postoperative complications in the remaining lobe (n = 3), positive pathological lymph node metastasis found by permanent section (n = 3), and malignancy in the remaining lobe (n = 5). The patients were divided into two groups according the interval between segmentectomy and completion lobectomy: group A (3-35 days, n = 5) and group B (56-1470 days, n = 6). There was a tendency for more severe adhesions around the hilum (p = 0.061) in group B, resulting in increased operative bleeding (p = 0.055), more usage of fibrin glue (p = 0.080), and significantly longer operative time (p = 0.036). Injury to the pulmonary arteries was experienced only in group B (3/6 cases). There was no operation-related mortality.
CONCLUSIONS: Completion lobectomy may become more difficult approximately 5 weeks after segmentectomy, due to severe adhesions, but it can be performed safely with careful manipulation.

PMID: 27207503 [PubMed - in process]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XJwddq
via IFTTT

Spheroid-Formation (Colonosphere) Assay for in Vitro Assessment and Expansion of Stem Cells in Colon Cancer.

Spheroid-Formation (Colonosphere) Assay for in Vitro Assessment and Expansion of Stem Cells in Colon Cancer.

Stem Cell Rev. 2016 May 20;

Authors: Shaheen S, Ahmed M, Lorenzi F, Nateri AS

Abstract
Colorectal cancers (CRCs) form a disorganized hierarchy of heterogeneous cell populations on which current chemotherapy regimens fail to exert their distinctive cytotoxicity. A small sub-population of poorly differentiated cancer stem-like cells (CSCs), also known as cancer initiating cells, may exhibit embryonic and/or adult stem-cell gene expression signatures. Self-renewal and survival signals are also dominant over differentiation in CSCs. However, inducers of differentiation exclusive to CSC may affect cellular pathways required for the formation and progression of a tumor, which are not utilized in normal adult stem-cells. Nevertheless, assays for targeting CSCs have been hindered by expanding and maintaining rare CSCs in vitro. However, CRC-CSCs are able to form floating spheroids (known as colonospheres) 3-dimentinionally (3D) in a serum-free defined medium. Therefore, great efforts have been paid to improve colonosphere forming assay as a preclinical model to study tumor biology and to conduct drug screening in cancer research. The 3D-colonosphere culture model may also represent in vivo conditions for the spontaneous aggregation of cancer cells in spheroids. This protocol describes the development of an enrichment/culture assay using CRC-CSCs to facilitate colorectal cancer research through immunofluorescence staining of colonospheres. We have developed colonospheres from HCT116 CRC cell line to compare and link CRC-CSC markers to the NANOG expression level using an immunofluorescence assay. Our data also show that the immunostaining assay of colonosphere is a useful method to explore the role and dynamics of CRC-CSCs division between self-renewal and cell lineage differentiation of cancer cells. In principle, this method is applicable to a variety of primary cells and cell lines of epithelial origin. Furthermore, this protocol may also allow screening of libraries of compounds to identify bona fide CRC-CSC differentiation inducers.

PMID: 27207017 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U6XL9t
via IFTTT

Development of a Low-Cost, Noninvasive, Portable Visual Speech Recognition Program.

Development of a Low-Cost, Noninvasive, Portable Visual Speech Recognition Program.

Ann Otol Rhinol Laryngol. 2016 May 19;

Authors: Kohlberg GD, Gal YK, Lalwani AK

Abstract
OBJECTIVES: Loss of speech following tracheostomy and laryngectomy severely limits communication to simple gestures and facial expressions that are largely ineffective. To facilitate communication in these patients, we seek to develop a low-cost, noninvasive, portable, and simple visual speech recognition program (VSRP) to convert articulatory facial movements into speech.
METHODS: A Microsoft Kinect-based VSRP was developed to capture spatial coordinates of lip movements and translate them into speech. The articulatory speech movements associated with 12 sentences were used to train an artificial neural network classifier. The accuracy of the classifier was then evaluated on a separate, previously unseen set of articulatory speech movements.
RESULTS: The VSRP was successfully implemented and tested in 5 subjects. It achieved an accuracy rate of 77.2% (65.0%-87.6% for the 5 speakers) on a 12-sentence data set. The mean time to classify an individual sentence was 2.03 milliseconds (1.91-2.16).
CONCLUSION: We have demonstrated the feasibility of a low-cost, noninvasive, portable VSRP based on Kinect to accurately predict speech from articulation movements in clinically trivial time. This VSRP could be used as a novel communication device for aphonic patients.

PMID: 27208007 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YNW6Ha
via IFTTT

Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses against squamous cell carcinoma.

Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses against squamous cell carcinoma.

Oral Oncol. 2016 Jun;57:54-60

Authors: Kondo Y, Ohno T, Nishii N, Harada K, Yagita H, Azuma M

Abstract
V domain-containing Ig suppressor of T-cell activation (VISTA)/PD-1H is a novel immune checkpoint molecule for regulating T-cell activation. We examined the effects of anti-VISTA mAb monotherapy and combination therapy with CTLA-4 or PD-1 blockade in a squamous cell carcinoma (SCCVII) model. VISTA monotherapy did not show clear tumor growth regression, but efficiently induced CD8(+) T cell activation by converting resting and exhausted cells into functional effector cells. VISTA monotherapy did not inhibit recruitment of regulatory T cells (Tregs) in the tumor microenvironment (TME). As an additional treatment to VISTA, CTLA-4 blockade, but not PD-1 blockade, elicited further tumor regression. The CTLA-4 and VISTA combination efficiently inhibited Treg recruitment and increased the ratios of both CD8 T/Treg and CD4 conventional T (Tcon)/Treg in the TME, whereas the PD-1 and VISTA combination dramatically increased tumor-recruiting CD8(+) T cells, but markedly reduced the Tcon/Treg ratio. Our results demonstrate that VISTA blockade efficiently converts CD8(+) T cells into functional effector T cells, but is not sufficient to regress tumor growth due to weak Treg suppression in the TME. Our results suggest that combined CTLA-4 and VISTA blockade is more efficacious than combined PD-1 and VISTA blockade for tumors like head and neck squamous cell carcinoma in which Treg-mediated immune regulation is dominant.

PMID: 27208845 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XpFu9S
via IFTTT

The telomere proteins in tumorigenesis and clinical outcomes of oral squamous cell carcinoma.

The telomere proteins in tumorigenesis and clinical outcomes of oral squamous cell carcinoma.

Oral Oncol. 2016 Jun;57:46-53

Authors: Benhamou Y, Picco V, Pagès G

Abstract
The "Hallmarks of Cancer" describe the ways by which cancer cells bypass homeostasis. Escape from replicative senescence is one of the earliest features of cancer cells. Maintenance of the telomeres through reactivation of telomerase was initially associated with replicative immortality in various cancers. The shelterin complex, a telomeric hexaprotein association, plays a key role in telomere maintenance and in the hallmarks of cancer. Some shelterin proteins are overexpressed in diverse cancers and can promote tumorigenesis in animal models. Shelterin can also have an impact on tumor size, tumor growth and resistance to treatment. Studies into the expression level of shelterin in oral squamous cell carcinoma (OSCC) report contradictory results. Moreover, the exact role of these proteins in OSCC tumorigenesis remains uncertain. In this review, we examined the data linking telomeres and hallmarks of OSCC. Furthermore, we examined the literature concerning telomeres and the clinical outcome of OSCC. Finally, we propose a model encompassing the role of shelterin proteins in oral tumorigenesis and treatment outcome.

PMID: 27208844 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/242LyWe
via IFTTT

Do we need 5-FU in addition to cisplatin for chemoradiation of locally advanced head-and-neck cancer?

Do we need 5-FU in addition to cisplatin for chemoradiation of locally advanced head-and-neck cancer?

Oral Oncol. 2016 Jun;57:40-45

Authors: Rades D, Seidl D, Janssen S, Bajrovic A, Hakim SG, Wollenberg B, Schild SE

Abstract
OBJECTIVES: To compare chemoradiation with cisplatin alone or cisplatin plus 5-FU for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN).
MATERIALS AND METHODS: The outcomes of 142 patients who received chemoradiation with cisplatin alone for locally advanced SCCHN were retrospectively compared to 170 patients who received cisplatin plus 5-fluorouracil (5-FU). The outcomes compared included loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and adverse events.
RESULTS: Although patients who received cisplatin alone had a significantly worse performance status, 81% of these patients completed planned chemotherapy compared to 73% of patients in the cisplatin plus 5-FU group (p=0.18). Radiotherapy breaks >1week were necessary in 14% and 23% of patients, respectively (p=0.09). The 5-year LRC rates were 69% after cisplatin alone and 68% after cisplatin plus 5-FU (p=0.71). The 5-year MFS rates were 72% and 62%, respectively (p=0.37), and 5-year OS rates were 60% and 45%, respectively (p=0.066). On multivariate analysis, cisplatin alone was significantly associated with improved OS (RR 1.35; 95%-CI 1.09-1.69; p=0.006). Nausea/vomiting, pneumonia/sepsis and late adverse events occurred more common in the cisplatin plus 5-FU group.
CONCLUSION: Given the limitations of a retrospective study, chemoradiation with cisplatin alone appeared associated with fewer adverse events and better OS than with cisplatin plus 5-FU in patients with locally advanced SCCHN. Thus, 5-FU in addition to cisplatin may be omitted for these patients. A randomized trial is warranted to confirm these findings.

PMID: 27208843 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XpFlmX
via IFTTT

Image guided surgery in the management of head and neck cancer.

Image guided surgery in the management of head and neck cancer.

Oral Oncol. 2016 Jun;57:32-39

Authors: Iqbal H, Pan Q

Abstract
Complete resection of head and neck tumors relies on palpation and visual inspection. Achieving a negative margin in remote locations in the head and neck region, especially in close proximity to critical structures, is often difficult to achieve. Positive resection margins in head and neck cancer are at high risk to develop recurrent disease and associated with poor prognosis. Near-infrared fluorescence-guided optical imaging is an emerging technology with the potential to move the surgical field forward and facilitate surgeons to visualize tumors in real-time intra-operatively. In this review, our focus is to discuss the recent advances and the potential application of near infrared (NIR) fluorescent-guided surgery in the management of head and neck cancer.

PMID: 27208842 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/242LCVR
via IFTTT

Third party assessment of resection margin status in head and neck cancer.

Third party assessment of resection margin status in head and neck cancer.

Oral Oncol. 2016 Jun;57:27-31

Authors: Ransohoff A, Wood D, Solomon Henry A, Divi V, Colevas A

Abstract
BACKGROUND: Definitive assessment of primary site margin status following resection of head and neck cancer is necessary for prognostication, treatment determination and qualification for clinical trials. This retrospective analysis determined how often an independent reviewer can assess primary tumor margin status of head and neck cancer resections based on review of the pathology report, surgical operative report, and first follow-up note alone.
METHODS: We extracted from the electronic medical record pathology reports, operative reports, and follow-up notes from head and neck cancer resections performed at Stanford Hospital. We classified margin status as definitive or not. We labeled any pathology report clearly indicating a positive, negative, or close (<5mm) margin as definitive. For each non-definitive pathology report, we reviewed the operative report and then the first follow-up note in an attempt to clarify margin status. We also looked for associations between non-definitive status and surgeon, year, and primary site.
RESULTS: 743 unique cases of head and neck cancer resection were extracted. We discarded 255 as non-head and neck cancer cases, or cases that did not involve a definitive resection of a primary tumor site. We could not definitively establish margin status in 20% of resections by independent review of the medical record. There was no correlation between margin determination and surgeon, site, or year of surgery.
CONCLUSION: A substantial fraction (20%) of primary site surgical margins could not be definitively determined via independent EMR review. This could have implications for subsequent patient care decisions and clinical trial options.

PMID: 27208841 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TnvVsJ
via IFTTT

Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11.

Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11.

Oral Oncol. 2016 Jun;57:21-26

Authors: Ward MC, Adelstein DJ, Bhateja P, Nwizu TI, Scharpf J, Houston N, Lamarre ED, Lorenz R, Burkey BB, Greskovich JF, Koyfman SA

Abstract
PURPOSE: The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the timing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) develops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of SLD after CRT.
METHODS: Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT between 1993 and 2013 were identified. Events occurring beyond 3months after treatment and suggestive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered SLD. The cumulative incidence of SLD and its components was quantified using Gray's competing risk analysis with recurrence or death considered competing risks.
RESULTS: Eighty-four patients were included with a median follow-up of 43months. The 5-year overall survival was 70% (95% CI 58-80%). No death was directly a result of treatment-induced late dysphagia. The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within 5years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred beyond five years from CRT.
CONCLUSIONS: SLD is common after CRT for larynx cancer and can occur beyond 5years from the end of treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death related to dysphagia is uncommon.

PMID: 27208840 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YNVGAF
via IFTTT

microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection.

microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection.

Oral Oncol. 2016 Jun;57:15-20

Authors: He Q, Chen Z, Cabay RJ, Zhang L, Luan X, Chen D, Yu T, Wang A, Zhou X

Abstract
OBJECTIVE: We previously performed a meta-analysis of microRNA profiling studies on head and neck/oral cancer (HNOC), and identified 11 consistently dysregulated microRNAs in HNOC. Here, we evaluate the diagnostic values of these microRNAs in oral tongue squamous cell carcinoma (OTSCC) using oral cytology samples.
MATERIALS AND METHODS: The levels of 11 microRNAs were assessed in 39 oral cytology samples (19 OTSCC and 20 normal subjects), and 10 paired OTSCC and adjacent normal tissues. The predictive power of these microRNAs was analyzed by receiver operating characteristic curve (ROC) and random forest (RF) model. A classification and regression trees (CART) model was generated using miR-21 and miR-375, and further validated using both independent oral cytology validation sample set (14 OTSCC and 11 normal subjects) and tissue validation sample set (12 paired OTSCC and adjacent normal tissues).
RESULTS: Differential expression of miR-21, miR-100, miR-125b and miR-375 was validated in oral cytology training sample set. Based on the RF model, the combination of miR-21 and miR-375 was selected which provide best prediction of OTSCC. A CART model was constructed using miR-21 and miR-375, and was tested in both oral cytology and tissue validation sample sets. A sensitivity of 100% and specificity of 64% was achieved in distinguishing OTSCC from normal in the oral cytology validation set, and a sensitivity of 83% and specificity of 83% was achieved in the tissue validation set.
CONCLUSION: The utility of microRNA from oral cytology samples as biomarkers for OTSCC detection is successfully demonstrated in this study.

PMID: 27208839 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XpEW45
via IFTTT

Validation of metabolic tumor volume as a prognostic factor for oral cavity squamous cell carcinoma treated with primary surgery.

Validation of metabolic tumor volume as a prognostic factor for oral cavity squamous cell carcinoma treated with primary surgery.

Oral Oncol. 2016 Jun;57:6-14

Authors: Zhang H, Seikaly H, Nguyen NT, Abele JT, Dziegielewski PT, Harris JR, O'Connell DA

Abstract
BACKGROUND: Despite the promise of metabolic tumor volume (MTV) as a risk-stratifying marker, the retrospective design of the initial study limits its generalizability. Therefore, this study sought to validate MTV as a prognostic factor for oral cavity squamous cell carcinoma (OCSCC) treated with primary surgery within an independent data set.
METHODS: The validation data set consisted of 42 patients diagnosed with OCSCC between 2008 and 2012. The original cohort consisted of 80 patients. MTV and SUVmax were calculated for the primary tumor and nodal metastasis separately, as well as combined. Before statistical analysis, MTV and SUVmax values were divided into intertertile thirds to allow for intergroup survival analysis. Validation analysis was conducted on the validation data set alone. Data from both cohorts were then combined (n=122) to increase statistical power.
RESULTS: An increase in combined MTV of 17.5cm(3) was associated with statistically significant increase in risk of disease recurrence (HR=19.2, p<0.001) and death (HR=9.2, p<0.05). Combined SUVmax failed to predict overall (HR=1.0, p>0.05) and disease-free survival (HR=1.0, p>0.05). Increase in the MTV of the primary tumor was associated with an increase in the risk of disease recurrence (HR=21.7, p=0.0001) and risk of death (HR=7.0, p=0.0001), while increase in the MTV of the locoregional neck metastasis was not (p>0.05). An MTV cutoff value of greater than 10.2cm(3) was found to significantly affect survival.
CONCLUSION: Due to the reproducibility of MTV findings, this study validates MTV as an independent prognostic factor for OCSCC treated with primary surgery.

PMID: 27208838 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/242M1aI
via IFTTT

Osteoradionecrosis in patients with salivary gland malignancies.

Osteoradionecrosis in patients with salivary gland malignancies.

Oral Oncol. 2016 Jun;57:1-5

Authors: Tucker JR, Xu L, Sturgis EM, Mohamed AS, Hofstede TM, Chambers MS, Lai SY, Fuller CD, Beadle B, Gunn GB, Hutcheson KA

Abstract
PURPOSE: The present study was undertaken to evaluate osteoradionecrosis (ORN) in patients with salivary gland malignancies (SGM) after treatment with radiation therapy.
MATERIALS AND METHODS: The medical records of 172 patients treated with radiation therapy for SGM during a 12-year period (August 2001 to November 2013) were reviewed. Incidence, time to event, staging and management of ORN were analyzed.
RESULTS: Of the 172 patients, 7 patients (4%) developed ORN (median latency: 19months, range: 4-72months). Of those 7 patients, 4 required major surgery, 1 required hyperbaric oxygen therapy (HBO), one required minor debridement, and one required conservative management. Total prescribed radiation dose varied from 50Gy (1 case) to 70Gy (1 case) among those patients who developed ORN, and radiotherapy was delivered postoperatively after osseous resection in 4 of 7 cases. Three of the 7 cases of ORN occurred after traumatic injury to the bone. Of the 7 patients who developed ORN, 3 had SGM of the major glands, 3 had other sites of the oral cavity, and 1 had a sinonasal location.
CONCLUSION: While the rate of ORN after radiotherapy for SGM was somewhat lower (4%) than previously published data on patients with squamous cell carcinomas of the head and neck treated with radiation therapy (8-14%), ORN necessitating major surgery remains a clinically significant, possible late effect of radiotherapy in SGM survivors. Location of SGM is very important, with cases that developed ORN disproportionally having primary disease arising in the oral cavity.

PMID: 27208837 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TnvyOX
via IFTTT

Loss of glycine receptors containing the α3 subunit compromises auditory nerve activity, but not outer hair cell function.

Loss of glycine receptors containing the α3 subunit compromises auditory nerve activity, but not outer hair cell function.

Hear Res. 2016 May 18;

Authors: Dlugaiczyk J, Hecker D, Neubert C, Buerbank S, Campanelli D, Becker CM, Betz H, Knipper M, Rüttiger L, Schick B

Abstract
Inhibitory glycine receptors containing the α3 subunit (GlyRα3) regulate sensory information processing in the CNS and retina. In previous work, we demonstrated the presence of postsynaptic GlyR alpha3 immunoreactivity at efferent synapses of the medial and lateral olivocochlear bundle in the organ of Corti; however, the role of these alpha3-GlyRs in auditory signalling has remained elusive. The present study analyzes distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) of knockout mice with a targeted inactivation of the Glra3 gene (Glra3(-/-)) and their wildtype littermates (Glra3(+/+)) before and seven days after acoustic trauma (AT; 4 to 16 kHz, 120 dB SPL, 1 h). Before AT, DPOAE thresholds were slightly, but significantly lower, and DPOAE amplitudes were slightly larger in Glra3(-/-) as compared to Glra3(+/+) mice. While click- and f-ABR thresholds were similar in both genotypes before AT, threshold-normalized click-ABR wave I amplitudes were smaller in Glra3(-/-) mice as compared to their wildtype littermates. Following AT, both the decrement of ABR wave I amplitudes and the delay of wave I latencies were more pronounced in Glra3(-/-) than Glra3(+/+) mice. Accordingly, correlation between early click-evoked ABR signals (0 to 2.5 ms from stimulus onset) before and after AT was significantly reduced for Glra3(-/-) as compared to Glra3(+/+) mice. In summary, these results show that loss of α3-GlyRs compromises suprathreshold auditory nerve activity, but not outer hair cell function.

PMID: 27208792 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YNVVvL
via IFTTT

End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.

End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.

Clin Chim Acta. 2016 May 18;

Authors: Kumar M, Mehra S, Thakar A, Shukla NK, Roychoudhary A, Sharma MC, Ralhan R, Chauhan SS

Abstract
INTRODUCTION: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and despite the improvement in treatment strategy, 5-year survival rates are about 50%. Identification of patients at high risk of recurrence may enable rigorous personalized post-treatment management. In an earlier proteomics study we identified End Binding Protein (EB1) to be overexpressed in OSCC. We investigated the diagnostic and prognostic significance of alterations in expression of EB1 in oral cancer.
METHODS: In this retrospective study, the expression of EB1 protein was evaluated in 259 OSCCs, 41 dysplasia, 166 hyperplasia and 126 normal tissues using immunohistochemistry and correlated with clinical-pathological parameters and prognosis of OSCC patients over a follow-up period of up to 91months.
RESULTS: Significant overexpression of cytoplasmic EB1 was observed in hyperplasia [p<0.001, OR=7.2, 95% CI=4.1-12.8], dysplasia (p<0.001, OR=21.8, CI=8.8-50.2) and OSCCs (p<0.001, OR=10.1, CI=5.8-17.4) in comparison with normal mucosa. Univariate analysis revealed cytoplasmic EB1 association with tumor grade, tumor size and recurrence of the disease. Kaplan Meier survival analysis of EB1 expression showed significantly reduced disease free survival (DFS) (p=0.003). Notably, OSCC patients showing cytoplasmic EB1 overexpression demonstrated significantly reduced DFS (p=0.004, HR=2.1).
CONCLUSION: EB1 overexpression is an early event in oral tumorigenesis and cytoplasmic EB1 accumulation is associated with poor prognosis and tumor recurrence in OSCC patients.

PMID: 27208742 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XpFvuv
via IFTTT

TRAF3 Signaling: Competitive Binding and Evolvability of Adaptive Viral Molecular Mimicry.

TRAF3 Signaling: Competitive Binding and Evolvability of Adaptive Viral Molecular Mimicry.

Biochim Biophys Acta. 2016 May 18;

Authors: Guven-Maiorov E, Keskin O, Gursoy A, VanWaes C, Chen Z, Tsai CJ, Nussinov R

Abstract
BACKGROUND: The tumor necrosis factor receptor (TNFR) associated factor 3 (TRAF3) is a key node in innate and adaptive immune signaling pathways. TRAF3 negatively regulates the activation of the canonical and non-canonical NF-κB pathways and is one of the key proteins in antiviral immunity.
SCOPE OF REVIEW: Here we provide a structural overview of TRAF3 signaling in terms of its competitive binding and consequences to the cellular network. For completion, we also include molecular mimicry of TRAF3 physiological partners by some viral proteins.
MAJOR CONCLUSIONS: By out-competing host partners, viral proteins aim to subvert TRAF3 antiviral action. Mechanistically, dynamic, competitive binding by the organism's own proteins and same-site adaptive pathogen mimicry follow the same conformational selection principles.
GENERAL SIGNIFICANCE: Our premise is that irrespective of the eliciting event - physiological or acquired pathogenic trait - pathway activation (or suppression) may embrace similar conformational principles. However, even though here we largely focus on competitive binding at a shared site, similar to physiological signaling other pathogen subversion mechanisms can also be at play.

PMID: 27208423 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Tnw0fS
via IFTTT

Development of a Low-Cost, Noninvasive, Portable Visual Speech Recognition Program.

Development of a Low-Cost, Noninvasive, Portable Visual Speech Recognition Program.

Ann Otol Rhinol Laryngol. 2016 May 19;

Authors: Kohlberg GD, Gal YK, Lalwani AK

Abstract
OBJECTIVES: Loss of speech following tracheostomy and laryngectomy severely limits communication to simple gestures and facial expressions that are largely ineffective. To facilitate communication in these patients, we seek to develop a low-cost, noninvasive, portable, and simple visual speech recognition program (VSRP) to convert articulatory facial movements into speech.
METHODS: A Microsoft Kinect-based VSRP was developed to capture spatial coordinates of lip movements and translate them into speech. The articulatory speech movements associated with 12 sentences were used to train an artificial neural network classifier. The accuracy of the classifier was then evaluated on a separate, previously unseen set of articulatory speech movements.
RESULTS: The VSRP was successfully implemented and tested in 5 subjects. It achieved an accuracy rate of 77.2% (65.0%-87.6% for the 5 speakers) on a 12-sentence data set. The mean time to classify an individual sentence was 2.03 milliseconds (1.91-2.16).
CONCLUSION: We have demonstrated the feasibility of a low-cost, noninvasive, portable VSRP based on Kinect to accurately predict speech from articulation movements in clinically trivial time. This VSRP could be used as a novel communication device for aphonic patients.

PMID: 27208007 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YNW6Ha
via IFTTT

A clinical study of multimodal treatment for orbital organ preservation in locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus.

A clinical study of multimodal treatment for orbital organ preservation in locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus.

Jpn J Clin Oncol. 2016 May 20;

Authors: Chen NX, Chen L, Wang JL, Wang JY, Yan F, Ma L, Zhang XX

Abstract
OBJECTIVE: This study aimed to investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life.
METHODS: Clinical data of 28 cases of patients with orbital involvement of T4b squamous cell carcinoma of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between May 2008 and September 2015 were retrospectively analysed. The treatment efficacy and side effects were assessed. The study included 18 male and 10 female patients. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy and/or epidermal growth factor receptor inhibitor. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 4. The overall survival rate, local control rate and rate of effective orbital preservation were calculated using the Kaplan-Meier method.
RESULTS: All patients completed the planned chemotherapy, and 27 (96.4%) of the patients completed the planned radiotherapy cycle. After the multimodal treatment, the 3-year overall survival, local control rate and rate of effective orbital preservation of the patients were 59.2%, 80.2% and 77.8%, respectively.
CONCLUSIONS: Multimodal treatment could preserve the orbital organs of patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates and improve the quality of life of patients with advanced squamous cell carcinoma of the nasal cavity and paranasal sinus, thus providing a new treatment option for these patients.

PMID: 27207888 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/242LJRg
via IFTTT

Afatinib against esophageal or head-and-neck cell squamous carcinoma: significance of activating oncogenic HER4 mutations in HNSCC.

Afatinib against esophageal or head-and-neck cell squamous carcinoma: significance of activating oncogenic HER4 mutations in HNSCC.

Mol Cancer Ther. 2016 May 20;

Authors: Nakamura Y, Togashi Y, Nakahara H, Tomida S, Banno E, Terashima M, Hayashi H, de Velasco MA, Sakai K, Fujita Y, Okegawa T, Nutahara K, Hamada S, Nishio K

Abstract
The prognosis for patients with advanced esophageal or head-and-neck squamous cell carcinoma (ESCC or HNSCC) remains poor, and the identification of additional oncogenes and their inhibitors is needed. In this study, we evaluated the sensitivities of several ESCC and HNSCC cell lines to HER inhibitors (cetuximab, erlotinib, and afatinib) in vitro and found two cell lines that were hypersensitive to afatinib. Sequence analyses for the afatinib-targeted HER family genes in the two cell lines revealed that one cell line had a previously reported activating EGFR L861Q mutation, while the other had a HER4 G1109C mutation of unknown function. No amplification of HER family genes was found in either of the two cell lines. The phosphorylation level of HER4 was elevated in the HER4 G1109C mutation-overexpressed HEK293 cell line, and the mutation had a transforming potential and exhibited tumorigenicity in an NIH3T3 cell line, indicating that this HER4 mutation was an activating oncogenic mutation. Afatinib dramatically reduced the phosphorylation level of EGFR or HER4 and induced apoptosis in the two cell lines. In vivo, tumor growth was also dramatically decreased by afatinib. In a database, the frequencies of HER family gene mutations in ESCC or HNSCC ranged from 0% to 5%. In particular, HER4 mutations have been found relatively frequently in HNSCC. Considering the addiction of cancer cells to activating oncogenic EGFR or HER4 mutations for proliferation, HNSCC or ESCC with such oncogenic mutations might be suitable for targeted therapy with afatinib.

PMID: 27207775 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XpF9Ej
via IFTTT

Exploring the bacterial assemblages along the human nasal passage.

Exploring the bacterial assemblages along the human nasal passage.

Environ Microbiol. 2016 May 21;

Authors: Wos-Oxley ML, Chaves-Moreno D, Jáuregui R, Oxley AP, Kaspar U, Plumeier I, Kahl S, Rudack C, Becker K, Pieper DH

Abstract
The human nasal passage, from the anterior nares through the nasal vestibule to the nasal cavities, is an important habitat for opportunistic pathogens and commensals alike. This work sampled four different anatomical regions within the human nasal passage across a large cohort of individuals (n= 79) comprising individuals suffering from chronic nasal inflammation clinically known as chronic rhinosinusitis (CRS) and individuals not suffering from inflammation (CRS-free). While individuals had their own unique bacterial fingerprint that was consistent across the anatomical regions, these bacterial fingerprints formed into distinct delineated groups comprising core bacterial members, which were consistent across all four swabbed anatomical regions irrespective of health status. The most significant observed pattern was the difference between the global bacterial profiles of swabbed and tissue biopsy samples from the same individuals, being also consistent across different anatomical regions. Importantly, no statistically significant differences could be observed concerning the global bacterial communities, any of the bacterial species or the range of diversity indices used to compare between CRS and CRS-free individuals, and between two CRS phenotypes (without nasal polyps and with nasal polyps). Thus, the role of bacteria in the pathogenesis of sinusitis remains uncertain. This article is protected by copyright. All rights reserved.

PMID: 27207744 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TnvX3G
via IFTTT

Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.

Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.

Carcinogenesis. 2016 Apr 28;

Authors: Sigurdson AJ, Brenner AV, Roach JA, Goudeva L, Müller JA, Nerlich K, Reiners C, Schwab R, Pfeiffer L, Waldenberger M, Braganza M, Xu L, Sturgis EM, Yeager M, Chanock SJ, Pfeiffer RM, Abend M, Port M

Abstract
Several single-nucleotide polymorphisms (SNPs) have been associated with papillary and follicular thyroid cancer (PTC and FTC, respectively) risk, but few have replicated. After analyzing 17525 tag SNPs in 1129 candidate genes, we found associations with PTC risk in SERPINA5, FTO, HEMGN (near FOXE1) and other genes. Here, we report results from a replication effort in a large independent PTC/FTC case-control study conducted in Germany. We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer. We genotyped 422 PTC and 130 FTC cases and 752 controls recruited from three German clinical centers. We used polytomous logistic regression to simultaneously estimate PTC and FTC associations for 79 SNPs based on log-additive models. We assessed effect modification by body mass index (BMI), gender and age for all SNPs, and selected SNP by SNP interactions. We confirmed associations with PTC and SNPs in FOXE1/HEMGN, SERPINA5 (rs2069974), FTO (rs8047395), EVPL (rs2071194), TICAM1 (rs8120) and SCARB1 (rs11057820) genes. We found associations with SNPs in FOXE1, SERPINA5, FTO, TICAM1 and HSPA6 and FTC. We found two significant interactions between FTO (rs8047395) and BMI (P = 0.0321) and between TICAM1 (rs8120) and FOXE1 (rs10984377) (P = 0.0006). Besides the known associations with FOXE1 SNPs, we confirmed additional PTC SNP associations reported previously. We also found several new associations with FTC risk and noteworthy interactions. We conclude that multiple variants and host factors might interact in complex ways to increase risk of PTC and FTC.

PMID: 27207655 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1YNVqSi
via IFTTT

Lipocalin 2 prevents oral cancer metastasis through carbonic anhydrase IX inhibition and is associated with favourable prognosis.

Lipocalin 2 prevents oral cancer metastasis through carbonic anhydrase IX inhibition and is associated with favourable prognosis.

Carcinogenesis. 2016 Apr 27;

Authors: Lin CW, Yang WE, Lee WJ, Hua KT, Hsieh FK, Hsiao M, Chen CC, Chow JM, Chen MK, Yang SF, Chien MH

Abstract
Lipocalin 2 (LCN2), a secreted glycoprotein, is up- or downregulated in different human cancers. At present, the functional role of LCN2 in the progression of oral squamous cell carcinoma (OSCC), which accounts for most head and neck cancers, remains poorly understood, particularly with respect to its involvement in invasion and metastasis. In this study, we observed that LCN2 expression decreased in patients with OSCC and lymph node metastasis compared with that in patients without metastasis. A higher LCN2 expression correlated with the survival of patients with OSCC. Furthermore, LCN2 overexpression in OSCC cells reduced in vitro migration and invasion and in vivo metastasis, whereas its silencing induced an increase in cell motility. Mechanistically, LCN2 inhibited the cell motility of OSCC cells through hypoxia-inducible factor (HIF)-1α-dependent transcriptional inhibition of the carbonic anhydrase IX (CAIX). CAIX overexpression relieved the migration inhibition imposed by LCN2 overexpression in OSCC cells. Moreover, a microRNA (miR) analysis revealed that LCN2 can suppress CAIX expression and cell migration through miR-4505 induction. Examination of tumour tissues from patients with OSCC and OSCC-transplanted mice revealed an inverse correlation between LCN2 and CAIX expression. Furthermore, patients with LCN2(strong)/CAIX(weak) revealed the lowest frequency of lymph node metastasis and the longest survival. Our findings suggest that LCN2 suppresses tumour metastasis by targeting the transcriptional and post-transcriptional regulation of CAIX in OSCC cells. LCN2 overexpression may be a novel OSCC treatment strategy and a useful biomarker for predicting OSCC progression.

PMID: 27207653 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/242LwO4
via IFTTT

Medial sural artery perforator flap in head and neck reconstruction.

Medial sural artery perforator flap in head and neck reconstruction.

Eur Arch Otorhinolaryngol. 2016 May 20;

Authors: Özkan HS, İrkören S, Aydın OE, Eryılmaz A, Karaca H

Abstract
Medial sural artery perforator (MSAP) flap is a relatively new flap which is a modification of medial gastrocnemius myocutaneous flap. Both radial forearm flap and MSAP has common benefits, such as thinness, long pedicle and pliability; however, MSAP has lower donor site morbidity when compared with radial forearm flap. Because of this reason, the MSAP flap has gained popularity during the last decade. The objective of this study was to determine clinical application results of this flap in reconstruction of post-oncologic defects in the head and neck region. 11 patients operated for head and neck post oncologic defects and reconstructed with MSAP between June 2014 and Dec 2015 were included in the study. Age, gender, histopathology, area of reconstruction, flap size, number of perforators were reviewed. Postoperatively recipient and donor site complications, hospital stay and additional surgical procedures were also analyzed. We had seven uncomplicated cases; one total flap failure due to arterial problem, in three cases due fistula formation and local wound healing problems additional surgeries were performed. All venous anastomosis were performed with 9/0 sutures, nine arterial anastomosis were performed with 9/0 and two arterial anastomosis were performed with 10/0 nylon sutures. Medial sural artery perforator flap is a good alternative in head and neck reconstruction, with the advantages of thin and pliable skin, a reliable vascular pedicle, straightforward intramuscular dissection. But there are certain drawbacks like tedious pedicle and perforator dissection, small arterial pedicle size which complicates anastomosis and obscurities of anatomy. Surgical team must always be ready for a difficult micro anastomosis and an alternative flap choice must be prepared and counseled with the patient in case of inadequate perforators.

PMID: 27207139 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/27N5XTR
via IFTTT

Current and Emerging Clinical Applications of Multispectral Optoacoustic Tomography (MSOT) in Oncology.

Current and Emerging Clinical Applications of Multispectral Optoacoustic Tomography (MSOT) in Oncology.

Clin Cancer Res. 2016 May 20;

Authors: McNally LR, Mezera M, Morgan DE, Frederick PJ, Yang ES, Eltoum IE, Grizzle WE

Abstract
Accurate detection and characterization of cancers is key for providing timely intervention and effective treatments. Current imaging technologies are particularly limited when it comes to detecting very small tumors in vivo, i.e. very early cancers or metastases, differentiating viable tumor from surrounding dead tumor tissue, and evaluating tumor metabolism within tissue. Optoacoustic imaging offers potential solutions to these imaging problems because of its ability to image optical absorption properties of both intrinsic tissue chromophores and exogenous contrast agents without the involvement of ionizing radiation. Optoacoustic imaging uses pulsed laser to induce localized thermoelastic expansion that generates acoustic waves detectable by an ultrasound transducer. To date, Multispectral optoacoustic tomography (MSOT) has primarily been utilized in preclinical research; however, its use in translational and clinical research is expanding. This review focuses on the current and emerging applications of optoacoustic imaging for the molecular imaging of cancer using both exogenous and endogenous contrast agents and sheds light on potential future clinical applications.

PMID: 27208064 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1qCnwEr
via IFTTT

High-risk and low-risk gastric cancer areas in Italy and its association with microsatellite instability.

High-risk and low-risk gastric cancer areas in Italy and its association with microsatellite instability.

J Cancer Res Clin Oncol. 2016 May 20;

Authors: Polom K, Marrelli D, Pascale V, Roviello G, Voglino C, Rho H, Vindigni C, Marini M, Macchiarelli R, Roviello F

Abstract
PURPOSE: The different pathological characteristics and prognoses between gastric cancer patients coming from high-risk (group A) and low-risk (group B) areas of Italy were analyzed. We investigated a suspected difference in microsatellite instability (MSI) between these two groups.
METHODS: MSI analyses of 452 gastric cancer patients were performed using five quasimonomorphic mononucleotide repeats NR-21, NR-24, NR-27, BAT-25, and BAT-26. MSI analysis was done by PCR usage. An allelic profile of these five mononucleotides was detected on an automated DNA sequencer ABI PRISM 3100 Genetic Analyser. Data were analyzed according to high-risk and low-risk gastric cancer areas.
RESULTS: MSI was observed in 23.9 % of all gastric cancer patients studied. Patients from group A showed a higher rate of MSI (28.4 %) than from group B (13.5 %) (p < 0.001). We analyzed this association together with tumor location and Lauren classification: A nonsignificant differences were seen when analyzing cardia and non-cardia tumors (p = 0.854) but significant for Lauren histotype (p = 0.028). There was no statistical difference in survival between high-risk and low-risk areas (p = 0.437), with a nonsignificant trend for better survival in the high-risk group, especially when measured over a longer period of time. Analyzing MSI or MSS in these groups, the survival curves were almost the same.
CONCLUSIONS: A higher frequency of MSI in patients coming from high-risk areas may help explain geographical differences in gastric cancer. The trend of better survival in high-risk areas may be due to a higher rate of MSI gastric cancer patients.

PMID: 27206556 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TAW3i7
via IFTTT

Antigenic characterization of influenza viruses produced using synthetic DNA and novel backbones

Publication date: Available online 21 May 2016
Source:Vaccine
Author(s): Pirada Suphaphiphat, Lynne Whittaker, Ivna De Souza, Rodney S. Daniels, Philip R. Dormitzer, John W. McCauley, Ethan C. Settembre
The global system for manufacturing seasonal influenza vaccines has been developed to respond to the natural evolution of influenza viruses, but the problem of antigenic mismatch continues to be a challenge in certain years. In some years, mismatches arise naturally due to the antigenic drift of circulating viruses after vaccine strain selection has already been made. In other years, antigenic differences between the vaccine virus and circulating viruses are introduced as part of the current system, which relies on the use of egg-adapted isolates as a starting material for candidate vaccine viruses (CVVs). Improving the current process for making vaccine viruses can provide great value. We have previously established a synthetic approach for rapidly generating influenza viruses in a vaccine-approved Madin Darby canine kidney (MDCK) cell line using novel, high-growth backbones that increase virus rescue efficiency and antigen yield. This technology also has the potential to produce viruses that maintain antigenic similarity to the intended reference viruses, depending on the hemagglutinin (HA) and neuraminidase (NA) sequences used for gene synthesis. To demonstrate this utility, we generated a panel of synthetic viruses using HA and NA sequences from recent isolates and showed by hemagglutination inhibition (HI) tests that all synthetic viruses were antigenically-like their conventional egg- or cell-propagated reference strains and there was no impact of the novel backbones on antigenicity. This synthetic approach can be used for the efficient production of CVVs that may be more representative of circulating viruses and may be used for both egg- and cell-based vaccine manufacturing platforms. When combined with mammalian cell culture technology for antigen production, synthetic viruses generated using HA and NA sequences from a non-egg-adapted prototype can help to reduce the potential impact of antigenic differences between vaccine virus and circulating viruses on vaccine effectiveness.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/20lZGsO
via IFTTT

A national examination of pharmacy-based immunization statutes and their association with influenza vaccinations and preventive health

Publication date: Available online 21 May 2016
Source:Vaccine
Author(s): Kevin W. McConeghy, Coady Wing
BackgroundA series of state-level statute changes have allowed pharmacists to provide influenza vaccinations in community pharmacies. The study aim was to estimate the effects of pharmacy-based immunization statutes changes on per capita influenza vaccine prescriptions, adult vaccination rates, and the utilization of other preventive health services.MethodsA quasi-experimental study that compares vaccination outcomes over time before and after states allowed pharmacy-based immunization. Measures of per capita pharmacy prescriptions for influenza vaccines in each state came from a proprietary pharmacy prescription database. Data on adult vaccination rates and preventive health utilization were studied using multiple waves of the Behavioral Risk Factor Surveillance System (BRFSS). The primary outcomes were changes in per capita influenza vaccine pharmacy prescriptions, adult vaccination rates, and preventive health interventions following changes.ResultsBetween 2007 and 2013, the number of influenza vaccinations dispensed in community pharmacies increased from 3.2 to 20.9 million. After one year, adopting pharmacist immunization statutes increased per capita influenza vaccine prescriptions by an absolute difference (AD) of 2.6% (95% CI: 1.1–4.2). Adopting statutes did not lead to a significant absolute increase in adult vaccination rates (AD 0.9%, 95% CI: −0.3, 2.2). There also was no observed difference in adult vaccination rates among adults at high-risk of influenza complications (AD 0.8%, 95% CI: −0.2, 1.8) or among standard demographic subgroups. There also was no observed difference in the receipt of preventive health services, including routine physician office visits (AD −1.9%, 95% CI: −4.9, 1.1).ConclusionsPharmacists are providing millions of influenza vaccines as a consequence of immunization statutes, but we do not observe significant differences in adult influenza vaccination rates. The main gains from pharmacy-based immunization may be in providing a more convenient way to obtain an important health service.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NEMMFb
via IFTTT

Report of the Cent Gardes HIV Vaccines Conference. Part 1: The antibody response; Fondation Mérieux Conference Center, Veyrier-du-Lac, France, 25–27 October 2015

Publication date: Available online 20 May 2016
Source:Vaccine
Author(s): Marc P. Girard, Roger Le-Grand, Valentina Picot, Christophe Longuet, Gary J. Nabel
The 2015 Cent Gardes Conference on HIV vaccines took place on October 25–27 at the Merieux Foundation Conference Center in Veyrier du Lac, near Annecy, France. The meeting reviewed progress in the development of HIV vaccines and identified new directions of future research. The field has advanced incrementally over the past year but major progress will require additional information from new clinical trials. In this article, we review the presentations on humoral immune responses to HIV, and highlight the difficulty of eliciting broadly neutralizing antibodies by vaccination. Advances in cellular immunity for HIV prevention will be reviewed separately, in a following article.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/20lZIRg
via IFTTT

The impact of implementing a demand forecasting system into a low-income country's supply chain

Publication date: Available online 21 May 2016
Source:Vaccine
Author(s): Leslie E. Mueller, Leila A. Haidari, Angela R. Wateska, Roslyn J. Phillips, Michelle M. Schmitz, Diana L. Connor, Bryan A. Norman, Shawn T. Brown, Joel S. Welling, Bruce Y. Lee
ObjectiveTo evaluate the potential impact and value of applications (e.g. ordering levels, storage capacity, transportation capacity, distribution frequency) of data from demand forecasting systems implemented in a lower-income country's vaccine supply chain with different levels of population change to urban areas.Materials and MethodsUsing our software, HERMES, we generated a detailed discrete event simulation model of Niger's entire vaccine supply chain, including every refrigerator, freezer, transport, personnel, vaccine, cost, and location. We represented the introduction of a demand forecasting system to adjust vaccine ordering that could be implemented with increasing delivery frequencies and/or additions of cold chain equipment (storage and/or transportation) across the supply chain during varying degrees of population movement.ResultsImplementing demand forecasting system with increased storage and transport frequency increased the number of successfully administered vaccine doses and lowered the logistics cost per dose up to 34%. Implementing demand forecasting system without storage/transport increases actually decreased vaccine availability in certain circumstances.DiscussionThe potential maximum gains of a demand forecasting system may only be realized if the system is implemented to both augment the supply chain cold storage and transportation. Implementation may have some impact but, in certain circumstances, may hurt delivery. Therefore, implementation of demand forecasting systems with additional storage and transport may be the better approach. Significant decreases in the logistics cost per dose with more administered vaccines support investment in these forecasting systems.ConclusionDemand forecasting systems have the potential to greatly improve vaccine demand fulfilment, and decrease logistics cost/dose when implemented with storage and transportation increases direct vaccines. Simulation modeling can demonstrate the potential health and economic benefits of supply chain improvements.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NEMTk4
via IFTTT

Humoral, T-cell and B-cell immune responses to seasonal influenza vaccine in solid organ transplant recipients receiving anti-T cell therapies

Publication date: Available online 21 May 2016
Source:Vaccine
Author(s): Delphine Héquet, Manuel Pascual, Sarah Lartey, Rishi D. Pathirana, Geir Bredholt, Katja Hoschler, Roger Hullin, Pascal Meylan, Rebecca J. Cox, Oriol Manuel
BackgroundWe analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globulins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients.Methods71 kidney and heart transplant recipients (basiliximab [n=43] and ATG [n=28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-γ ELISpot assays and intracellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot.ResultsMedian time of vaccination from transplantation was 29 months (IQR 8–73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group (p=0.44, p=0.61, and p=0.21, respectively). The number of influenza-specific IFN-γ-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/10⁶ PBMC, p=0.0007), but no differences between treatment groups were observed (p=0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p=0.94; H3N2 p=0.34; B, p=0.79), irrespective of the type of anti-T-cell therapy.ConclusionsAfter influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/20m076n
via IFTTT

Effectiveness of seasonal trivalent influenza vaccination against hospital-attended acute respiratory infections in pregnant women: A retrospective cohort study

Publication date: Available online 20 May 2016
Source:Vaccine
Author(s): Annette K. Regan, Nicholas de Klerk, Hannah C. Moore, Saad B. Omer, Geoffrey Shellam, Paul V. Effler
BackgroundPregnant women are at risk of serious influenza infection. Although previous studies indicate maternal influenza vaccination can prevent hospitalisation in young infants, there is limited evidence of the effect in mothers.MethodsA cohort of 34,701 pregnant women delivering between 1 April 2012 and 31 December 2013 was created using birth records. Principal diagnosis codes from hospital emergency department (ED) and inpatient records were used to identify episodes of acute respiratory illness (ARI) during the 2012 and 2013 southern hemisphere influenza seasons. Cox regression models were used to calculate adjusted hazard ratios (aHRs) by maternal vaccination status, controlling for Indigenous status, socioeconomic level, medical conditions, and week of delivery.Results3,007 (8.7%) women received a seasonal influenza vaccine during pregnancy. Vaccinated women were less likely to visit an ED during pregnancy for an ARI (9.7 visits per 10,000 person-days vs. 35.5 visits per 10,000 person-days; aHR: 0.19, 95% CI: 0.05−0.68). Vaccinated women were also less likely to be hospitalised with an ARI compared to unvaccinated women (16.2 hospitalisations per 10,000 person-days vs. 34.0 hospitalisations per 10,000 person-days; aHR: 0.35, 95% CI: 0.13−0.97).ConclusionsInfluenza vaccination during pregnancy was associated with significantly fewer hospital attendances for ARI in pregnant women.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1NEMyOo
via IFTTT